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k j and d were
2021-10-20
15k, 15j and 14d, were then submitted to metabolic stability studies in human and mouse liver microsomes and permeability test with Caco-2 cells (Table 7). 15k, 15j and 14d all retained excellent permeability (Papp value greater than 15.2 × 10−6 cm/s) and displayed modestly improved metabolic stabil
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Because of its role in
2021-10-19
Because of its role in the cleavage of Aβ and the fact that many genetic forms of AD are caused by mutations in the enzyme, GS has long been a target for drug development, though previous clinical trials of Semagacestat, a GS inhibitor, have failed due to an increase in skin cancer, and a decrease i
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The overall very satisfactory potency profile of compounds
2021-10-19
The overall very satisfactory potency profile of compounds 7a–l suggests that 1,3,4-thiadiazole-2-carboxamide moiety was a suitable periphery group to add to the 3-phenylpropanoic Irinotecan HCl Trihydrate core in order to improve affinity to FFA1. The agonist activity in this series appears to be
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Species specificity of small molecular GPR agonists have bee
2021-10-19
Species specificity of small molecular GPR40 agonists have been reported by Takeda scientist. In the binding pocket of TM5, a Leu186 in human GPR40/FFA1 is replaced with Phe in rat, resulting in dramatic inter-species GPR40 activity discrepancy in certain scaffolds of small molecular GPR40 agonists.
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Polyunsaturated fatty acids PUFAs represent a class of lipid
2021-10-19
Polyunsaturated fatty acids (PUFAs) represent a class of lipids that contain two or more carbon double (unsaturated) bonds (CC) and classified as n-3, n-6 and n-9 fatty acids. PUFAs including n-3 such as docosahexaenoic Amikacin (DHA), eicosapentaenoic acid (EPA) and n-6 such as arachidonic acid (A
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Liver and muscle isozymes have
2021-10-19
Liver and muscle isozymes have been found in vertebrate tissues [2], [5], [6]. The liver FBPase is recognized as a regulatory enzyme of gluconeogenesis. The muscle isozyme participates in the glycogen synthesis from lactate and in the regulation of glycolysis [7], [8], [9]. The basic difference betw
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br Conclusion br Acknowledgements This work was
2021-10-19
Conclusion Acknowledgements This work was supported by R01 HL127386 (Niklason) and 1R01 HL128406-01A1 (Dardik), and by an unrestricted research gift from Humacyte Inc. KLL was supported by F30HL143880. KLL and EQ were supported by T32 GM007205. LEN is a founder and shareholder in Humacyte, Inc
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It has been reported that the
2021-10-19
It has been reported that the FDP synthase in Hevea latex has a major role to produce the starter substrate FPP for the prenyl chain elongation in natural rubber biosynthesis (Takaya et al., 2003). Accumulation of HbFDP mRNA transcripts in different tissue types including latex (natural rubber) prod
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br Venous thromboembolism VTE is a rare but potentially life
2021-10-19
Venous thromboembolism (VTE) is a rare but potentially life-threatening complication of total joint arthroplasty (TJA) . With modern chemoprophylaxis, the incidence of VTE after primary total hip (THA) or total knee (TKA) arthroplasty is commonly estimated between 0.5% and 1%, and VTE is now consi
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Management of HIV treatment with HIV PIs can
2021-10-19
Management of HIV-1 treatment with HIV PIs can be complicated due to wide inter-patient variability in Spadin levels. In certain scenarios, therapeutic drug monitoring (TDM) has been recommended as a useful approach to individualize therapy for HIV-infected patients [[9], [10], [11], [12]]. Several
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In the present study fasting blood glucose and insulin
2021-10-19
In the present study, fasting blood glucose and insulin levels were not significantly different between GA patients and control cases. Normal mammalian cells typically acquire fatty acids from the circulation owing to insulin, which is the most lipogenic hormone in the subset of adult tissues, inclu
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We found statistically significant association between p HER
2021-10-19
We found statistically significant association between p95-HER2 levels and hormone receptor status, Ki-67 dilution formula and metastatic regions (p = 0.004, 0.05) and the median OS was 27.66 months versus 24.02 months for p95-HER2 positive and p95-HER2 negative BC patients respectively (p > 0.05)
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In summary P P macrocyclization
2021-10-19
In summary, P2-P4 macrocyclization proved to be an effective strategy to drive activity in this series of HCV NS3 protease inhibitors while microsomal stability was enhanced by the introduction of steric bulk along the tether. This modification augmented the previously-described tactic of improving
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Lactate LA the end product of aerobic glycolysis has
2021-10-19
Lactate (LA), the end product of aerobic glycolysis, has been long neglected and seen as a byproduct until recently the findings for its important role in global gene transcription, cancer progression, functional polarisation of immune ALW-II-41-27 and the sustenance of stem cells [[7], [8], [9]]. L
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The synthesized methoxyamide derivatives were evaluated for
2021-10-19
The synthesized -methoxyamide derivatives were evaluated for in vitro as GPR119 agonists (, , ) whereas GSK1292263 (II in ) was used as the reference standard. To identify novel sulfone or tetrazole surrogates, diverse functional groups including amide, -sulfonyl amide, hydrazide, -methoxy--methyla
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